RARITAN, N.J., Nov. 3, 2022 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson are committed to redefining treatment outcomes in the hematology setting and today announced that abstracts from more than 50 company-sponsored studies, plus more than 20 investigator-initiated studies, will be presented at the American Society of Hematology (ASH) Annual Meeting in New Orleans from December 10-13, 2022. Janssen's commitment to advancing an innovative portfolio of therapies for healthcare professionals and patients is evidenced through more than 70 presentations that span clinical studies and real-world data. In addition, this year's ASH press program will feature data from the Phase 1/2 MonumenTAL-1 talquetamab (GPRC5DxCD3 bispecific antibody) study in relapsed or refractory multiple myeloma (RRMM), and the Plenary Scientific Session will highlight results from an investigator-initiated study of IMBRUVICA® (ibrutinib) in mantle cell lymphoma (MCL) on December 11. "Janssen's robust presence at ASH reflects a long-term commitment to discover and develop innovative, transformative therapies for patients with cancer," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "Recognizing the significant unmet needs that continue to persist in the treatment of hematologic malignances, we have never been more determined and dedicated in our mission to deliver cures." "In addition to developing innovative medicines, we are committed to listening, learning, and ultimately understanding the needs of the blood cancer community," said Tyrone Brewer, U.S. President, Oncology, Janssen Biotech, Inc. "Our commitment to patients runs deep, and we look forward to sharing Janssen's clinical data as well as learnings from our real-world evidence studies to help us advance patient care and enable healthcare professionals to make more informed treatment decisions." More than 35 presentations will highlight data from a robust pipeline and portfolio addressing the heterogeneity of this disease.
In the treatment of RRMM, highlights will include:
Updated results from the Phase 1 MonumenTAL-1 study of talquetamab and the first results from the Phase 2 portion of the MonumenTAL-1 study will be featured in the ASH press program and as an oral presentation (Abstract #157). Quality-of-life data from the same study will be highlighted in a poster presentation (Abstract #1937). Investigational data from the Phase 1/2 MajesTEC-1 trial of patients who received the approved dose of 1.5 mg/kg weekly of TECVAYLI™ will be featured in an oral presentation (Abstract #97). Poster presentations on pharmacokinetic (PK) analyses will provide further insight into patient responses from the MajesTEC-1 study (Abstract #1911, Abstract #3228). A new analysis supporting CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) will include minimal residual disease (MRD) negativity results from the Phase 1/2 CARTITUDE-1 study (Abstract #2030), and updated results from the Phase 2 CARTITUDE-2 study evaluating CARVYKTI® in patients who relapse early from their frontline therapy (Cohort B, Abstract #3354) and patients previously treated with an anti-BCMA agent (Cohort C, Abstract #2028). Longer-term follow-up data from the CARTIFAN-1 study in relapsed or refractory patients from China will also be presented (Abstract #3357). Oral presentations will feature patient-reported outcomes (PRO) with DARZALEX® treatment in NDMM. The presentations will highlight health-related quality of life (HRQoL) for transplant-eligible patients following treatment with DARZALEX® in combination with bortezomib, lenalidomide and dexamethasone (RVd) as part of the investigational GRIFFIN study (Abstract #473), and HRQoL for a subgroup of frail, transplant-ineligible patients who were treated with DARZALEX® in combination with lenalidomide and dexamethasone (Rd) in the MAIA study (Abstract #472). Poster presentations will highlight updated progression-free survival (PFS), overall survival (OS) and MRD data from the Phase 3 MAIA study of DARZALEX®-Rd compared to Rd alone, for the treatment of newly diagnosed patients who are ineligible for autologous stem cell transplant (ASCT) (Abstract #4559). Additional presentations will highlight post-hoc subgroup analyses of the MAIA study by patient type, including age (Abstract #4553) and high-risk cytogenetics (Abstract #3245). Updated six-year OS data from the ALCYONE study of DARZALEX® in combination with bortezomib, melphalan and prednisone (VMP) in transplant-ineligible patients will be featured in a poster presentation (Abstract #4561). Data from the final analysis of the investigational Phase 2 GRIFFIN study will provide updates on the use of DARZALEX®-RVd in Black patients who are newly diagnosed and transplant eligible (Abstract #4560). Highlights from the final analysis of the GRIFFIN study were featured in the plenary session at the 19th International Myeloma Society Annual Meeting. Advancing Science to Address Unmet Needs with IMBRUVICA® The data to be presented at ASH will add to the robust clinical and real-world data supporting IMBRUVICA®; studies include: The first presentation in the ASH Plenary Session will feature Phase 3 data from a study sponsored by the University of Munich and conducted by the European MCL Network of IMBRUVICA® combination therapy in younger patients with untreated MCL who are eligible for ASCT. Follow-up data from the Phase 3 GLOW study evaluating residual disease dynamics among newly diagnosed patients with CLL with unmutated IGHV or TP53 mutations when treated with fixed-duration Ibr + Ven versus chlorambucil plus obinutuzumab (Clb + O) (Abstract #93). Five-year follow-up data of efficacy and safety outcomes in patients with undetectable MRD in the MRD Cohort of the Phase 2 CAPTIVATE study (Abstract #92).
A comparative real-world evidence (RWE) oral presentation will report findings comparing time-to-next treatment in previously untreated patients with CLL receiving treatment with IMBRUVICA® or acalabrutinib (Abstract #797). Results from an all-payers claims database analysis will highlight prevalence and incidence data for multiple myeloma at the national level, by race, ethnicity, payer type, and state in an oral presentation (Abstract #384). Insights on the burden of hospitalization before and after disease progression following triple-class exposure in patients with relapsed and refractory multiple myeloma will be presented as a poster (Abstract #2284). A de novo poster presentation on the mode of action and pharmacology of nipocalimab in cells and preclinical models will examine the mechanistic relationship between nipocalimab concentration, FcRn occupancy, and inhibition of immunoglobulin G antibody (IgG) recycling (Abstract #3645). A Trial in Progress (TiP) poster presentation of the ENERGY study will highlight the rationale and study design for an adaptive, Phase 2/3 multicenter, randomized, double-blind, placebo-controlled study in patients with wAIHA with the aim to evaluate the efficacy and safety of nipocalimab compared with placebo (Abstract #1013). The TiP poster was previously accepted and presented at ASH 2021 and was modified to include updated information relating to the study design. A third abstract that was accepted for publication-only assessed the PK and pharmacodynamics of single doses of nipocalimab administered at different intravenous infusion rates in healthy adults (Abstract #4959). This abstract was previously accepted and presented at the 27th Congress of the European Hematology Association (EHA) 2022 and was modified to include PK data. A complete list of Janssen-sponsored abstracts is available at Janssen.com/ASH2022.
Talquetamab is a first-in-class, off-the-shelf, investigational T-cell redirecting bispecific antibody targeting both GPRC5D, a novel multiple myeloma target that does not shed over time, and CD3, a primary component of the T-cell receptor.2 CD3 is involved in activating T-cells, and GPRC5D is highly expressed on multiple myeloma cells.3,4 Talquetamab, which is given by subcutaneous injection, is currently being evaluated in a Phase 1/2 clinical study for the treatment of relapsed or refractory multiple myeloma (NCT03399799) and is also being explored in combination studies (NCT04586426, NCT05455320) and in a randomized Phase 3 study (NCT05461209). In January 2021, talquetamab was granted PRIME designation by the European Commission. In May 2021, and August 2021, talquetamab was granted Orphan Drug Designation for the treatment of multiple myeloma by the U.S. FDA and the European Commission, respectively. Talquetamab was also granted Breakthrough Therapy Designation from the U.S. FDA in June 2022 for the treatment of adult patients with relapsed or refractory multiple myeloma, who have previously received at least four prior lines of therapy, including a proteasome inhibitorproteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. TECVAYLI™ (teclistamab-cqyv) received approval from the U.S. FDA in October 2022 as an off-the-shelf (or ready to use) antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitorproteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.5 TECVAYLI™ is a first-in-class, bispecific T-cell engager antibody therapy which uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.6 For more information, visit www.CARVYKTI.com.
DARZALEX® (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.9 IMBRUVICA® is approved in more than 100 countries and has been used to treat more than 270,000 patients worldwide. There are more than 50 company-sponsored clinical trials, including 18 Phase 3 studies, and more than 11 years evaluating the efficacy and safety of IMBRUVICA®. *Accelerated approval was granted for MCL and MZL based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials. For more information, visit www.IMBRUVICA.com.
Nipocalimab is a high affinity, fully human, aglycosylated, effectorless anti-FcRn IgG1 monoclonal antibody being studied for autoantibody-driven conditions including generalized myasthenia gravis in children and adults, chronic inflammatory demyelinating polyneuropathy, hemolytic diseases of the fetus and newborn, warm autoimmune hemolytic anemia, Sjögren's syndrome, systemic lupus erythematosus, idiopathic inflammatory myopathies, and rheumatoid arthritis.15, 16, 17, 18, 19, 20, 21, 22, 23, 24 Nipocalimab targets FcRn, which plays a central role in prolonging the half–life of IgG autoantibodies.15 Blockade of this receptor has the potential to reduce overall IgG autoantibody levels without widespread immune suppression. In 2019, nipocalimab received Fast Track Designation for wAIHA.1 This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Cytokine Release Syndrome - TECVAYLI™ can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI™ at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI™. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation). Initiate therapy according to TECVAYLI™ step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI™ accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI™ based on severity. TECVAYLI™ is available only through a restricted program under a REMS. - TECVAYLI™ can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI™ at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI™. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI™ based on severity per recommendations and consider further management per current practice guidelines. Due to the potential for neurologic toxicity, patients are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI™ step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves. TECVAYLI™ is available only through a restricted program under a REMS. TECVAYLI™ REMS - TECVAYLI™ is available only through a restricted program under a REMS called the TECVAYLI™ REMS because of the risks of CRS and neurologic toxicity, including ICANS. Hepatotoxicity - TECVAYLI™ can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI™ at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI™ or consider permanent discontinuation of TECVAYLI™ based on severity. Monitor immunoglobulin levels during treatment with TECVAYLI™ and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis. Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI™ based on severity. Hypersensitivity and Other Administration Reactions - TECVAYLI™ can cause both systemic administration-related and local injection-site reactions. Systemic Reactions - In patients who received TECVAYLI™ at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue. Local Reactions - In patients who received TECVAYLI™ at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients, with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI™ or consider permanent discontinuation of TECVAYLI™ based on severity. Embryo-Fetal Toxicity - Based on its mechanism of action, TECVAYLI™ may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI™ and for 5 months after the last dose. Adverse Reactions - The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets. , including Boxed WARNING, for TECVAYLI™. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI®. Provide supportive care and/or corticosteroids as needed. Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI®. CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS Program. Cytokine Release Syndrome (CRS) including fatal or life-threatening reactions, occurred following treatment with CARVYKTI® in 95% (92/97) of patients receiving ciltacabtagene autoleucel. Grade 3 or higher CRS (2019 ASTCT grade) occurred in 5% (5/97) of patients, with Grade 5 CRS reported in 1 patient. The median time to onset of CRS was 7 days (range: 1‑12 days). The most common manifestations of CRS included pyrexia (100%), hypotension (43%), increased aspartate aminotransferase (AST) (22%), chills (15%), increased alanine aminotransferase (ALT) (14%) and sinus tachycardia (11%). Grade 3 or higher events associated with CRS included increased AST and ALT, hyperbilirubinemia, hypotension, pyrexia, hypoxia, respiratory failure, acute kidney injury, disseminated intravascular coagulation, HLH/MAS, angina pectoris, supraventricular and ventricular tachycardia, malaise, myalgias, increased C‑reactive protein, ferritin, blood alkaline phosphatase and gamma-glutamyl transferase. Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS. Monitor patients at least daily for 10 days following CARVYKTI® infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. Neurologic toxicities, which may be severe, life-threatening or fatal, occurred following treatment with CARVYKTI®. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of parkinsonism, Guillain-Barré Syndrome, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time. Overall, one or more subtypes of neurologic toxicity described below occurred following ciltacabtagene autoleucel in 26% (25/97) of patients, of which 11% (11/97) of patients experienced Grade 3 or higher events. These subtypes of neurologic toxicities were also observed in two ongoing studies. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Patients may experience fatal or life-threatening ICANS following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. ICANS occurred in 23% (22/97) of patients receiving ciltacabtagene autoleucel including Grade 3 or 4 events in 3% (3/97) and Grade 5 (fatal) events in 2% (2/97). The median time to onset of ICANS was 8 days (range 1-28 days). All 22 patients with ICANS had CRS. The most frequent (≥5%) manifestation of ICANS included encephalopathy (23%), aphasia (8%) and headache (6%). Monitor patients at least daily for 10 days following CARVYKTI® infusion at the REMS‑certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. Parkinsonism: Of the 25 patients in the CARTITUDE-1 study experiencing any neurotoxicity, five male patients had neurologic toxicity with several signs and symptoms of parkinsonism, distinct from immune effector cell-associated neurotoxicity syndrome (ICANS). Neurologic toxicity with parkinsonism has been reported in other ongoing trials of ciltacabtagene autoleucel. Patients had parkinsonian and non-parkinsonian symptoms that included tremor, bradykinesia, involuntary movements, stereotypy, loss of spontaneous movements, masked facies, apathy, flat affect, fatigue, rigidity, psychomotor retardation, micrographia, dysgraphia, apraxia, lethargy, confusion, somnolence, loss of consciousness, delayed reflexes, hyperreflexia, memory loss, difficulty swallowing, bowel incontinence, falls, stooped posture, shuffling gait, muscle weakness and wasting, motor dysfunction, motor and sensory loss, akinetic mutism, and frontal lobe release signs. The median onset of parkinsonism in the 5 patients in CARTITUDE-1 was 43 days (range 15-108) from infusion of ciltacabtagene autoleucel. Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson's disease, for the improvement or resolution of parkinsonism symptoms following CARVYKTI® treatment. Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS. REMS: Because of the risk of CRS and neurologic toxicities, CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS. Further information is available at www.CARVYKTIrems.com or 1-844-672-0067.
Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI® infusion. One patient underwent autologous stem cell therapy for hematopoietic reconstitution due to prolonged thrombocytopenia. In CARTITUDE-1, 30% (29/97) of patients experienced prolonged Grade 3 or 4 neutropenia and 41% (40/97) of patients experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Day 30 following ciltacabtagene autoleucel infusion. Recurrent Grade 3 or 4 neutropenia, thrombocytopenia, lymphopenia and anemia were seen in 63% (61/97), 18% (17/97), 60% (58/97), and 37% (36/97) after recovery from initial Grade 3 or 4 cytopenia following infusion. After Day 60 following ciltacabtagene autoleucel infusion, 31%, 12% and 6% of patients had a recurrence of Grade 3 or higher lymphopenia, neutropenia and thrombocytopenia, respectively, after initial recovery of their Grade 3 or 4 cytopenia. Eighty‑seven percent (84/97) of patients had one, two, or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Six and 11 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death. Monitor blood counts prior to and after CARVYKTI® infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines. Monitor patients for signs and symptoms of infection before and after CARVYKTI® infusion and treat patients appropriately. Administer prophylactic, pre-emptive and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 10% of patients after ciltacabtagene autoleucel infusion, and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated. Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV), or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice. Hypogammaglobulinemia was reported as an adverse event in 12% (12/97) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 92% (89/97) of patients. Monitor immunoglobulin levels after treatment with CARVYKTI® and administer IVIG for IgG Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI® treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CARVYKTI® treatment, and until immune recovery following treatment with CARVYKTI®. Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline, or neuropathy, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI® infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery during this initial period, and in the event of new onset of any neurologic toxicities. The most common non-laboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections of unspecified pathogen, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common laboratory adverse reactions (incidence greater than or equal to 50%) include thrombocytopenia, neutropenia, anemia, aminotransferase elevation, and hypoalbuminemia. As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitorproteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent Hypersensitivity and Other Administration Reactions
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®. In a pooled safety population of 898 patients with multiple myeloma (N=705) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 9% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 1%). Systemic administration-related reactions occurred in 8% of patients with the first injection, 0.3% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 140 systemic administration-related reactions that occurred in 77 patients, 121 (86%) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients. Severe reactions included hypoxia, dyspnea, hypertension and tachycardia. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritis, chills, vomiting, nausea, and hypotension. Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions. Cardiac Toxicity in Patients with Light Chain (AL) Amyloidosis
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets. Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose. Interference with Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®. Interference with Determination of Complete Response
Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein. The most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, pyrexia, cough, muscle spasms, back pain, vomiting, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema. As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitorproteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent Infusion-Related Reactions
DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life‑threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision. When DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: ® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion. Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®. Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®. DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets. Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein. Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose. The most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory infection, neutropenia, infusion‑related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX® are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia. click here to see the full Prescribing Information.
Hemorrhage: Fatal bleeding events have occurred in patients who received IMBRUVICA®. Major hemorrhage (≥ Grade 3, serious, or any central nervous system events; e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) occurred in 4.2% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA® in 27 clinical trials. Bleeding events of any grade including bruising and petechiae occurred in 39%, and excluding bruising and petechiae occurred in 23% of patients who received IMBRUVICA®, respectively. The mechanism for the bleeding events is not well understood.
Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA® increases the risk of major hemorrhage. Across clinical trials, 3.1% of 2,838 patients who received IMBRUVICA® without antiplatelet or anticoagulant therapy experienced major hemorrhage. The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4%, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1%. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA®. Monitor for signs and symptoms of bleeding. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding. Cardiac Arrhythmias, Cardiac Failure, and Sudden Death: Fatal and serious cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA®. Deaths due to cardiac causes or sudden deaths occurred in 1% of 4,896 patients who received IMBRUVICA® in clinical trials, including in patients who received IMBRUVICA® in unapproved monotherapy or combination regimens. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities. Patients with cardiac comorbidities may be at greater risk of these events. Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. Obtain further evaluation (e.g., ECG, echocardiogram) as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Manage cardiac arrhythmias and cardiac failure appropriately, follow dose modification guidelines, and consider the risks and benefits of continued IMBRUVICA® treatment. Hypertension: Hypertension occurred in 19% of 1,476 patients who received IMBRUVICA® in clinical trials. Grade 3 or greater hypertension occurred in 8% of patients. Based on data from 1,124 of these patients, the median time to onset was 5.9 months (range, 0.03 to 24 months). Monitor blood pressure in patients treated with IMBRUVICA®, initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA® as appropriate, and follow dosage modification guidelines for Grade 3 or higher hypertension. Cytopenias: In 645 patients with B-cell malignancies who received IMBRUVICA® as a single agent, grade 3 or 4 neutropenia occurred in 23% of patients, grade 3 or 4 thrombocytopenia in 8% and grade 3 or 4 anemia in 2.8%, based on laboratory measurements. Monitor complete blood counts monthly. Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMBRUVICA® and for 1 month after the last dose. Advise males with female partners of reproductive potential to use effective contraception during the same time period. Approximately 9% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of adult patients had a dose reduction due to adverse reactions. Approximately 4-10% (CLL/SLL), 9% (MCL), and 7% (WM [5%] and MZL [13%]) of patients discontinued due to adverse reactions. cGVHD: The most common adverse reactions (≥20%) in adult or pediatric patients with cGVHD were fatigue (57%), anemia (49%)*, bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, musculoskeletal pain (30%), pyrexia (30%), muscle spasms (29%), stomatitis (29%), hemorrhage (26%), nausea (26%), abdominal pain (23%), pneumonia (23%), and headache (21%). The most common Grade 3 or higher adverse reactions (≥5%) reported in adult or pediatric patients with cGVHD were pneumonia (14%), anemia (13%)*, fatigue (12%), pyrexia (11%), diarrhea (10%), neutropenia (10%)*, sepsis (10%), osteonecrosis (9%), stomatitis (9%), hypokalemia (7%), headache (5%), and musculoskeletal pain (5%). Discontinuation of IMBRUVICA® treatment due to an adverse reaction occurred in 24% of adult patients and 23% of pediatric patients. Adverse reactions leading to dose reduction occurred in 26% of adult patients and 19% of pediatric patients. *Treatment-emergent decreases (all grades) were based on laboratory measurements.
CYP3A Inhibitors: Co-administration of IMBRUVICA® with strong or moderate CYP3A inhibitors may increase ibrutinib plasma concentrations. Increased ibrutinib concentrations may increase the risk of drug-related toxicity. Dose modifications of IMBRUVICA® are recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. Avoid concomitant use of other strong CYP3A inhibitors. Interrupt IMBRUVICA® if strong inhibitors are used short-term (e.g., for ≤ 7 days). Avoid grapefruit and Seville oranges during IMBRUVICA® treatment, as these contain strong or moderate inhibitors of CYP3A. See dose modification guidelines in USPI sections 2.3 and 7.1. CYP3A Inducers: Avoid coadministration with strong CYP3A inducers. Pediatric Use: The safety and effectiveness of IMBRUVICA® have not been established for the treatment of cGVHD after failure of one or more lines of therapy in pediatric patients less than 1 year of age. The safety and effectiveness of IMBRUVICA® in pediatric patients have not been established in MCL, CLL/SLL, CLL/SLL with 17p deletion, WM, MZL or in patients with mature B-cell non-Hodgkin lymphoma. In the randomized population from a study that included 35 patients (26 pediatric patients age 5 to less than 17 years) with previously treated mature B-cell non-Hodgkin lymphoma, major hemorrhage and discontinuation of chemoimmunotherapy due to adverse reactions occurred more frequently in the ibrutinib plus chemoimmunotherapy arm compared to the chemoimmunotherapy alone arm. Adult Patients with B-cell Malignancies: Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA® in patients with severe hepatic impairment. In patients with mild or moderate impairment, reduce recommended IMBRUVICA® dose and monitor more frequently for adverse reactions of IMBRUVICA®. Patients with cGVHD: Avoid use of IMBRUVICA® in patients with total bilirubin level > 3x upper limit of normal (ULN) (unless of non-hepatic origin or due to Gilbert's syndrome). Reduce recommended dose when administering IMBRUVICA® to patients with total bilirubin level > 1.5 to 3x ULN (unless of non-hepatic origin or due to Gilbert's syndrome). Please click here to see the full Prescribing Information.
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